Ginger has been used for centuries in Ayurvedic and traditional Chinese medicine to treat inflammation. In the United States, ginger dietary supplement use for arthritis treatment has received increased attention since the removal of COX-2 inhibitors from the market. However, very little scientific data is available regarding possible anti- arthritic effects of ginger or its components and interpretation of existing data is difficult because test materials were not adequately described. Therefore, no information is currently available to support the use of ginger dietary supplements for arthritis prevention or treatment. Our proposed studies will fill this void, taking advantage of an on-going successful collaboration between Dr. J Funk, an expert in the use of animal models for the study of inflammation, and Dr. B Timmermann, an expert natural products chemist. Based on our preliminary data demonstrating an profound anti-arthritic effect of two well characterized ginger extracts, the specific aims of this project are to (1) isolate and chemically and biologically characterize a crude ginger extract which will then be tested in vivo using an animal model of rheumatoid arthritis, a particularly severe form of inflammatory arthritis, to determine (2) the anti-arthritic efficacy of the crude ginger extract when administered orally as a dietary supplement, as well as (3) its potential toxicity and (4) mechanisms of joint-protective action. PUBLIC HEALTH RELEVANCE: Information obtained from these translational studies will form an evidence base to guide the public's rational use and choice of ginger dietary supplements for the treatment of joint inflammation in rheumatoid arthritis and aid in the design of future appropriate clinical trials. Moreover, mechanistic evidence of bone protective effects of ginger may also support the study of its use for the prevention of other prevalent bone diseases, such as osteoporosis.